Institut de Cardiologie, CHU Pitié-Salpêtrière (AP-HP), Université Paris 6, Paris, France.
Lancet. 2011 Aug 20;378(9792):693-703. doi: 10.1016/S0140-6736(11)60876-3.
Primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction has traditionally been supported by unfractionated heparin, which has never been directly compared with a new anticoagulant using consistent anticoagulation and similar antiplatelet strategies in both groups. We compared traditional heparin treatment with intravenous enoxaparin in primary PCI.
In a randomised open-label trial, patients presenting with ST-elevation myocardial infarction were randomly assigned (1:1) to receive an intravenous bolus of 0·5 mg/kg of enoxaparin or unfractionated heparin before primary PCI. Wherever possible, medical teams travelling in mobile intensive care units (ambulances) selected, randomly assigned (using an interactive voice response system at the central randomisation centre), and treated patients. Patients who had received any anticoagulant before randomisation were excluded. Patients and caregivers were not masked to treatment allocation. The primary endpoint was 30-day incidence of death, complication of myocardial infarction, procedure failure, or major bleeding. The main secondary endpoint was the composite of death, recurrent acute coronary syndrome, or urgent revascularisation. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00718471.
910 patients were assigned to treatment with enoxaparin (n=450) or unfractionated heparin (n=460). The primary endpoint occurred in 126 (28%) patients after anticoagulation with enoxaparin versus 155 (34%) patients on unfractionated heparin (relative risk [RR] 0·83, 95% CI 0·68-1·01, p=0·06). The incidence of death (enoxaparin, 17 [4%] vs heparin, 29 [6%] patients; p=0·08), complication of myocardial infarction (20 [4%] vs 29 [6%]; p=0·21), procedure failure (100 [26%] vs 109 [28%]; p=0·61), and major bleeding (20 [5%] vs 22 [5%]; p=0·79) did not differ between groups. Enoxaparin resulted in a significantly reduced rate of the main secondary endpoint (30 [7%] vs 52 [11%] patients; RR 0·59, 95% CI 0·38-0·91, p=0·015). Death, complication of myocardial infarction, or major bleeding (46 [10%] vs 69 [15%] patients; p=0·03), death or complication of myocardial infarction (35 [8%] vs 57 [12%]; p=0·02), and death, recurrent myocardial infarction, or urgent revascularisation (23 [5%] vs 39 [8%]; p=0·04) were all reduced with enoxaparin.
Intravenous enoxaparin compared with unfractionated heparin significantly reduced clinical ischaemic outcomes without differences in bleeding and procedural success. Therefore, enoxaparin provided an improvement in net clinical benefit in patients undergoing primary PCI.
Direction de la Recherche Clinique, Assistance Publique-Hôpitaux de Paris; Sanofi-Aventis.
ST 段抬高型心肌梗死的传统经皮冠状动脉介入治疗（PCI）一直采用未分级肝素支持，这种方法从未与新型抗凝药物进行过直接比较，两组的抗凝和抗血小板策略也不一致。我们比较了传统肝素治疗与直接 PCI 中的依诺肝素静脉给药。
在一项随机开放标签试验中，ST 段抬高型心肌梗死患者被随机（1:1）分配接受 0.5mg/kg 的依诺肝素或未分级肝素静脉推注，然后进行直接 PCI。只要可能，来自移动重症监护单元（救护车）的医疗团队选择、随机分配（使用中央随机化中心的交互式语音响应系统）并治疗患者。在随机分组前接受过任何抗凝治疗的患者被排除。患者和护理人员对治疗分配不知情。主要终点是 30 天内的死亡率、心肌梗死并发症、手术失败或大出血。主要次要终点是死亡、复发性急性冠状动脉综合征或紧急血运重建的复合终点。分析采用意向治疗。该试验在 ClinicalTrials.gov 注册，编号为 NCT00718471。
910 名患者被分配接受依诺肝素（n=450）或未分级肝素（n=460）治疗。抗凝后依诺肝素组 126 名（28%）患者发生主要终点事件，未分级肝素组 155 名（34%）患者发生主要终点事件（相对风险 [RR]0.83，95%CI0.68-1.01，p=0.06）。依诺肝素组 17 名（4%）患者发生死亡，肝素组 29 名（6%）患者发生死亡（p=0.08）；依诺肝素组 20 名（4%）患者发生心肌梗死并发症，肝素组 29 名（6%）患者发生心肌梗死并发症（p=0.21）；依诺肝素组 100 名（26%）患者手术失败，肝素组 109 名（28%）患者手术失败（p=0.61）；依诺肝素组 20 名（5%）患者发生大出血，肝素组 22 名（5%）患者发生大出血（p=0.79）。依诺肝素组主要次要终点发生率显著降低（30 名 [7%] vs 52 名 [11%]患者；RR0.59，95%CI0.38-0.91，p=0.015）。依诺肝素组死亡、心肌梗死并发症或大出血（46 名 [10%] vs 69 名 [15%]患者；p=0.03）、死亡或心肌梗死并发症（35 名 [8%] vs 57 名 [12%]患者；p=0.02）以及死亡、复发性心肌梗死或紧急血运重建（23 名 [5%] vs 39 名 [8%]患者；p=0.04）均减少。
与未分级肝素相比，依诺肝素静脉给药显著降低了临床缺血性结局，且出血和手术成功率无差异。因此，依诺肝素在接受直接 PCI 的患者中提供了更好的净临床获益。
临床研究指导部，巴黎公立医院集团；赛诺菲安万特。
